Menthol is one of most important flavor or fragrance substances providing a cooling sensation. In most cases, however, it has still been isolated from natural supply sources by crystallization. In addition to natural menthol, in order to produce 1-menthol ((1R,2S,5R)-menthol) on an industrial scale, it is necessary to enhance the economy of its synthesis process as much as possible. For this purpose, particularly the synthesis of 1-menthol from inexpensive achiral raw materials is a problem to be solved.
This 1-menthol can be synthesized according to two concepts. According to one of the concepts, it is produced by esterifying racemic menthol obtained, for example, by hydrogenation of thymole, followed by racemic resolution (by crystallization or enzymatic resolution) (refer to Patent Documents 1 and 2).
According to the other concept, S. Akutagawa describes the synthesis of 1-menthol by enantioselective isomerization from allylamine to enamine by using rhodium-BINAP (BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) as a catalyst (refer to Non-patent Document 1).
On the other hand, there is disclosed a method of asymmetrically synthesizing 1-menthol including, as an important stage thereof, enantioselective hydrogenation of piperitenone (refer to Patent Document 3).
There is also disclosed a method for manufacturing an optically active menthol from geraniol, nerol, or a mixture of geraniol and nerol, including a) asymmetrically hydrogenating geraniol, nerol, or a mixture of geraniol and nerol to thereby obtain an optically active citronellol, b) oxidizing the resulting optically active citronellol to thereby obtain an optically active citronellal, c) conducting a ring-closure of the resulting optically active citronellal to thereby obtain a mixture containing an optically active isopulegol, and taking out the optically active isopulegol from the resulting mixture, and then, d) hydrogenating it to thereby obtain an optically active menthol (refer to Patent Document 4).
There is also disclosed a method for manufacturing optically active menthol from geranial, neral, or a mixture of geranial and neral, including a) subjecting citral (a mixture of geranial and neral) to precision distillation to thereby obtain geranial or neral, b) asymmetrically hydrogenating the resulting geranial or neral to thereby obtain an optically active citronellal, c) conducting a ring-closure of the resulting optically active citronellal to thereby obtain a mixture containing an optically active isopulegol and taking out the optically active isopulegol from the resulting mixture, and then, d) hydrogenating it to thereby obtain an optically active menthol (refer to Patent Document 5).
Isopulegol is an important intermediate for synthesizing racemic menthol and optically active menthol. It is typically prepared by a ring-closing oxo-ene reaction of citronellal in the presence of a Lewis acid catalyst. It is typically obtained as a mixture of four diastereomers, that is, isopulegol, iso-isopulegol, neo-isopulegol, and neoiso-isopulegol. As a method of preparing isopulegol which is important among them with high selectivity, there is disclosed a method of ring-closing citronellal in the presence of an aluminum catalyst (refer to Patent Documents 6 to 10).